Invasion of experimental rat brain tumor: early morphological changes following microinjection of C6 glioma cells (original) (raw)
Summary
We present morphological data of the early stage of tumor invasion in the central nervous system. C6 rat glioma cells were injected into the caudate-putamen of rat brain using glass micropipettes to minimize traumatic reactions. Four days after the inoculation, we examined the tumor-brain interface using light and electron microscopy. Ultrastructurally the tumor processes were attached to the perivascular basement membrane instead of the astroglial end-feet. At the tumor periphery, the vessel walls were in contact with both tumor processes and astroglial end-feet. Astrocytes withdrew their processes from the vascular walls and changed into a reactive phenotype, while the neuronal cells remained virtually intact, even when surrounded by tumor cells. Immunohistochemical study using C6 cells labeled with bromodeoxyuridine showed migration of the cells toward the perviascular space that was distant from the site of injection. These observations represent the earliest morphologically detectable changes of the tumor-brain interface, and suggest that the C6 cells possess the characteristics of high affinity to the endothelial basement membrane and invade along the preexisting blood vessels with brain parenchymal infiltration.
Access this article
Subscribe and save
- Get 10 units per month
- Download Article/Chapter or eBook
- 1 Unit = 1 Article or 1 Chapter
- Cancel anytime Subscribe now
Buy Now
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Instant access to the full article PDF.
Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.
References
- Auer RN, Del Maestro RF, Anderson R (1981) A simple and reproducible experimental in vivo glioma model. Can J Neurol Sci 8: 325–331
Google Scholar - Barde YA, Lindsay RM, Monard D, Thoenen H (1978) New factor released by cultured glioma cells supporting survival and growth of sensory neurons. Nature 274: 818
Google Scholar - Barker M, Hoshino T, Gurcay O, Wilson CB, Nielson SL, Downie R, Eliason J (1973) Development of an animal brain tumor model and its response to therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res 33: 976–986
Google Scholar - Benda P, Lightbody J, Sato G, Levine L, Sweet W (1968) Differentiated rat glial cell strain in tissue culture. Science 161: 370
Google Scholar - Bernstein JJ, Getz R, Jefferson M, Kelemen M (1985) Astrocytes secrete basal lamina after hemisection of rat spinal cord. Brain Res 327: 135–141
Google Scholar - Bissell MG, Rubinstein LJ, Bignami A, Herman MM (1974) Characteristics of the rat C-6 glioma maintained in organ culture systems. Production of glial fibrillary acidic protein in the absence of gliofibrillogenesis. Brain Res 82: 77–89
Google Scholar - Carter WG, Wayner EA, Bouchard TS, Kaur P (1990) The role of integrins α2β1, and α3β1 in cell-cell and cell-substrate adhesion of human epithelial cells. J Cell Biol 110: 1387–1404
Google Scholar - Cerame MA, Guthikonda M, Kohli CM (1985) Extraneural metastasis in gliosarcoma: a case report and review of the literature. Neurosurgery 17: 413–418
Google Scholar - Couldwell WT, de Tribolet N, Antel JP, Gauthier T, Kuppner MC (1992) Adhesion molecules and malignant gliomas: implications for tumorigenesis. J Neurosurg 76: 782–791
Google Scholar - Eng LR, Reier PJ, Houle JD (1987) Astrocyte activation and fibrous gliosis: glial fibrillary acidic protein immunostaining of astrocyte following intraspinal cord grafting of fetal CNS tisue. Prog Brain Res 71: 439–445
Google Scholar - Farrell CL, Stewart PA, Del Maestro RF (1987) A new glioma model in rat: the C6 spheroid implantation technique permeabiligy and vascular characterization. J Neurooncol 4: 403–415
Google Scholar - Hürter T, Mennel HD (1981) Experimental brain tumors and edema in rats. I. Histology and cytology of tumors. Acta Neuropathol (Berl) 55: 105–111
Google Scholar - Jänisch W, Schreiber D (1977) Methods of induction of experimental CNS tumors. In: Binger DD, Swenberg JA (eds), Experimental tumors of the central nervous system, 1st English edn. The UpJohn Co, Kalamazoo, pp 16–41
Google Scholar - Jones PA, De Clerck YA (1982) Extracellular matrix destruction by invasive tumor cells. Cancer Metastasis Rev 1: 289–297
Google Scholar - Kleihues P, Lantos PL, Magee PN (1976) Chemical carcinogenesis in the nervous system. Int Rev Exp Pathol 15: 153–232
Google Scholar - Klein G, Klien E (1985) Evolution of tumours and the impact of molecular oncology. Nature 315: 190–195
Google Scholar - Lantos PL, Pilkington GJ (1979) The development of experimental brain tumours. A sequential light and electron microscope study of the subependymal plate. I. Early lesions (abnormal cell clusters). Acta Neuropathol (Berl) 45: 167–175
Google Scholar - Liepkalns VA, Icard-Liepkalns C, Sommer AM, Quigley JP (1982) Properties of cloned human glioblastima cells. J Neurol Sci 57: 257–264
Google Scholar - Lindsay RM (1986) Reactive gliosis. In: Federoff S, Vernadakis A (eds) Astrocytes, vol. 3. Academic Press, New York, pp 231–262
Google Scholar - Manthorpe MM, Rudge JS, Varon S (1986) Astroglial cell contributions to neuronal survival and neuritic growth. In: Federoff S, Vernadakis A (eds) Astrocytes, vol 3. Academic Press, New York, pp 315–376
Google Scholar - Mareel MM, Bracke ME, Boghaert ER (1986) Tumor invasion and metastasis: therapeutic implications? Radiother Oncol 6: 135–142
Google Scholar - Mørk S, Laerum OD, de Ridder L (1984) Invasiveness of tumours of the central nervous system. In: Mareel MM, Calman K (eds) Tumor invasion. Oxford University Press, New York, pp 79–125
Google Scholar - Murray KJ, Chou SN, Douglas SD (1976) Topographical anatomy of human cerebral and cerebellar astrocytomas in vitro. Surg Neurol 6: 337–340
Google Scholar - Nicolson GL (1982) Cancer metastasis: organ colonization and the cell-surface properties of malignant cells. Biochim Biophys Acta 695: 113–176
Google Scholar - Paganetti PA, Caroni P, Schwab ME (1988) Glioblastoma infiltration into central nervous system tissue in vitro: involvement of a metalloprotease. J Cell Biol 107: 2281–2291
Google Scholar - Parker KK, Norenberg MD, Vernadakis A (1980) “Transdifferentiation” of C6 glial cells in culture. Science 208: 179–181
Google Scholar - Pauli BU, Schwartz DE, Thonar EJ-M, Kuettner KE (1983) Tumor invasion and host extracellular matrix. Cancer Metastasis Rev 2: 129–152
Google Scholar - Reier PJ (1986) Gliosis following CNS injury: the anatomy of astrocytic scars and their influences on axonal elongation. In: Federoff S, Vernadakis A (eds) Astrocytes, vol 3. Academic Press, New York, pp 263–324
Google Scholar - Rutka JT (1986) Effects of extracellular matrix proteins on the growth and differentiation of an anaplastic glioma cell line. Can J Neurol Sci 13: 301–306
Google Scholar - Rutka JT, Apodaka G, Stern R, Rosenblum M (1988) The extracellular matrix of the central and peripheral nervous system: structure and function. J Neurosurg 69: 155–170
Google Scholar - Sasaki H, Sato F, Mannen H (1989) Morphological analysis of single astrocytes of the adult cat central nervous system visualized by HRP microinjection. Brain Res 501: 339–354
Google Scholar - Schwartz MS, Morris J, Sarid J (1991) Overexpression of oncogene products can cause tumor progression without parenchymal infiltration in the rat brain. Cancer Res 51: 3595–3601
Google Scholar - Shabad LM (1973) Precancerous morphologic lesions. J Natl Cancer Inst 50: 1421–1428
Google Scholar - Spence AM, Coates PW (1978) Scanning electron microscopy of cloned astrocytic lines derived from ethylnitrosoureainduced rat gliomas. Virchows Arch [B] 28: 77–85
Google Scholar - Stewart PA, Hayakawa K, Hayakawa E, Farrell CL, Del Maestro RF (1985) A quantitative study of blood-brain barrier permeability ultrastructure in a new rat glioma model. Acta Neuropathol (Berl) 67: 96–102
Google Scholar
Author information
Authors and Affiliations
- Department of Neurosurgery, Tokyo Medical and Dental University School of Medicine, 1-5-45, Yushima, Bunkyoku, Tokyo, Japan
Nobuhisa Nagano, Masaru Aoyagi & Kimiyoshi Hirakawa - Department of Anatomy, Tokyo Medical and Dental University School of Medicine, 1-5-45, Yushima, Bunkyoku, Tokyo, Japan
Hiroshi Sasaki
Authors
- Nobuhisa Nagano
- Hiroshi Sasaki
- Masaru Aoyagi
- Kimiyoshi Hirakawa
Rights and permissions
About this article
Cite this article
Nagano, N., Sasaki, H., Aoyagi, M. et al. Invasion of experimental rat brain tumor: early morphological changes following microinjection of C6 glioma cells.Acta Neuropathol 86, 117–125 (1993). https://doi.org/10.1007/BF00334878
- Received: 26 June 1992
- Revised: 08 March 1993
- Accepted: 12 March 1993
- Issue Date: July 1993
- DOI: https://doi.org/10.1007/BF00334878